During the reporting year, the NCGC worked with over 300 researchers worldwide to advise them on assay design and development, chemistry research, informatics research, technology development projects, and to run high-throughput screens and chemically optimize small molecule leads. In collaboration with the Molecular Libraries Probe Production Centers Network (MLPCN), the U.S. Environmental Protection Agency, the National Toxicology Program, NIEHS, FDA, NCI, numerous rare disease foundations, and other intramural and extramural laboratories, the NCGC performed over 34 high-throughput screens on molecular targets and cellular phenotypes important for virtually every area of biology and disease. The NCGC also continued its work in the field of siRNA, initiating assay development on 14 projects, completing 12 pilot screens (1,000 genes), completing 12 primary screens (7,000 genes) and initiating 14 others, and moving into hit validation and follow-up on those projects. 13 new chemical probes of diverse biologies were discovered, and NCGC scientists published 56 publications during FY12. The NCGC filed 8 patent applications during this reporting period. Also during the reporting period, the NCGC deposited 243 BioAssays, 27 Summary AIDs, 13,143,171 concentration response curves, and a total of 52,572,684 data points into PubChem. NCGC continued to apply its chemistry expertise to optimizing probes; a portfolio of 19 in-house chemistry projects and 18 chemistry collaborations was maintained throughout the year. Under leadership from NCGC, along with the U.S. Environmental Protection Agency and the National Toxicology Program of NIEHS, the Toxicology in the 21st Century project (Tox21) continued to flourish. Tox21 is an initiative designed to predict the toxicity of chemicals on human health and the environment. This is accomplished by developing in vitro assays for more predictive, mechanistically-based methods than those used with current animal testing. During FY12, Tox21 continued its accelerated production phase. In the current reporting year, NCGC completed 26 full Tox21 screens and 45 smaller-scale screens on specific, varied cell lines. Given the NCGC's continual efficiency improvement program, we were able to increase the throughput of existing robotic screening, informatics, and chemistry systems by improvements in applications, software, and utilization scheduling, driven by both the project teams and Project Management. The NCGC maintained its existing robotic technology and Bio Safety Levels 1, 2, and 3 facilities during the reporting period. In addition, Sam Michael, head of the HTS and Robotics Core at NCGC, won the 2012 NIH Federal Engineer of the Year award. The NCGC's Outreach program continued its extraordinary record of productivity during the reporting period. NCGC staff advised 219 outside investigators on assay design and assay development, and assisted over 50 investigators with chemistry, informatics, and technology development inquiries. NCGC scientists gave 72 invited presentations throughout the U.S., Europe, and Asia during the period. NCGC outreach resulted in the submission of over 74 grant applications for NIH programs. The NCGC website was completely redesigned and consolidated with the TRND program to form the new NCATS website (ncats.nih.gov). The Assay Guidance manual has continued to evolve and has become a central resource for investigators interested in MLPCN science. During the reporting period, 73,967 visits were recorded, with 144,942 page views, and 54,504 unique visitors. 56% of these visitors originated from outside the US, from a total of 157 countries. 72% of visits were new visits, indicating that a large number of new users are finding the Assay Guidance Manual site. The manual remains a central resource for investigators interested in MLPCN science. During the year, the NCGC also maintained its status as an active member of the NCI's Chemical Biology Consortium and currently has one project in progress. NCGC continued work on its induced pluripotent stem (iPS) cell grant. In addition, NCGC continued to work on its NIH Directors Challenge Award for malaria research. Finally, NCGC's work on its IATAP grants continued.